Biomedical subjects

Albert Mimran

Publications and source records attributed to Albert Mimran.

18 recordsLinked to original sources

PubMed2006

Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study.

Diabetic nephropathy has developed into a worldwide epidemic and is responsible for the majority of end-stage renal disease in most countries. Antihypertensive treatment slows the progression of the disease. In addition, blockade of the renin-angiotensin system reduces the degree of albuminuria and angiotensin II receptor blockers (ARBs) have been shown to delay the progression from microalbuminuria to overt proteinuria in patients with diabetes. However, few studies have examined whether the initial stage of diabetic nephropathy (i.e. the development of microalbuminuria) in patients with type 2 diabetes can be slowed or prevented by ARB treatment. The Randomised Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP) study is a placebo-controlled, multicentre, double-blind, parallel group study investigating the effect of the ARB, olmesartan medoxomil, on the incidence of microalbuminuria. A total of 4400 type 2 diabetes patients with normoalbuminuria will be randomized to treatment with 40 mg of olmesartan medoxomil once daily or placebo. Goal blood pressure will be 130/80 mmHg. The primary endpoint of the study is the occurrence of microalbuminuria. In ROADMAP, we will also assess as secondary endpoints the effects of olmesartan on fatal and non-fatal cardiovascular events in patients with diabetes. In addition, within subgroups of the ROADMAP patients, the effects of olmesartan on retinopathy and other microvascular circulations will be analysed. The study is expected to last a median of 5 years. The ROADMAP study will answer the question whether an ARB can prevent or delay the onset of microalbuminuria and whether this translates into protection against cardiovascular events and renal disease.

Adolescent↗

PubMed2006

Consequences of elevated pulse pressure on renal function.

Peripheral pulse pressure (PP) is a marker of aging-associated arterial stiffening after the fifth decade. In addition, PP has emerged as a strong predictor of cardiovascular morbidity and mortality. A study of the relationship between renal function and aging of the arterial system using reliable methods of estimating renal haemodynamics (effective renal plasma flow) and function (glomerular filtration rate; GFR) was thus undertaken in a large number of never-treated individuals with essential hypertension. In 212 patients with isolated systolic hypertension, there was an inverse correlation between GFR and PP, but the correlation did not persist after adjustment for age. In fact, the deleterious effect of PP on GFR was observed, independent of age and mean arterial pressure, only in patients aged 60 years and over. In contrast, no clear influence of PP on GFR was detected in patients aged 40 years and over but less than 60 years and in those younger than 40 years. It is thus proposed that PP may have a detrimental influence on the age-related decline in GFR. Prospective studies on the influence of antihypertensive agents with possible effects on peripheral and central PP on the progressive decline of GFR are required.

Age Factors↗

PubMed2005

Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats.

Reversal by the mineralocorticoid receptor antagonist spironolactone on cardiac and renal abnormalities, associated with long-term (since weaning) administration of a high (2 and 8% NaCl chow, HS2 and HS8) sodium diet, was assessed in Sprague-Dawley rats. At the age of 5 mo, spironolactone (20 or 100 mg/kg, gavage) or placebo were given for 14 days to HS2 and HS8 rats. A group fed a regular diet (0.8% NaCl, NS) remained untreated. High sodium intake had no detectable effect on blood pressure; however, cardiac mass index and cross-sectional area of the carotid artery, as well as albuminuria, were increased only in the HS8 group compared with the control group on NS diet. In addition, a marked reduction in glomerular filtration rate (by 40%), associated with a nonproportional fall in renal plasma flow (thus resulting in a decrease in filtration fraction), was observed only in the HS8 group. No change in cardiac and renal fibrosis was detected. Production of the reactive oxygen species (ROS) by aortic tissue was increased in HS8 rats, whereas ROS production by the heart was unaffected. Only the high dose of spironolactone was effective, as it markedly reversed the cardiac hypertrophy and renal hypofiltration associated with the HS8 feeding. The changes were observed in the absence of any effect on systemic blood pressure and production of ROS. These observations favor aldosterone's role in the deleterious effects of marked and prolonged increases in sodium intake.

Administration, Oral↗

PubMed2005

Relative glomerular hyperfiltration in primary aldosteronism.

Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and 131I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and beta2 microglobulin were higher in PA than EH (88 +/- 26 versus 39 +/- 12 and 0.91 +/- 0.23 versus 0.26 +/- 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 +/- 3/13 +/- 2 mmHg), urinary excretion of albumin and beta2 microglobulin (by 48 +/- 19 and 0.53 +/- 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 +/- 3 and 54 +/- 15 ml/min per 1.73 m(2), respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.

Adenoma↗

PubMed2005

Elevated pulse pressure is associated with low renal function in elderly patients with isolated systolic hypertension.

In the past decade, pulse pressure has emerged as a strong predictor of cardiovascular morbidity and mortality. During aging, elevation of pulse pressure is a consequence of stiffening of the arterial wall. The relationship between pulse pressure and the renal aging process was studied in a cohort of 212 patients with never-treated isolated systolic hypertension. Glomerular filtration rate and effective renal plasma flow were measured using constant infusion of technetium 99m (99mTc)-DTPA and 131I-ortho-iodohippurate, respectively, and timed urine collections. The relationship between pulse pressure and renal function was studied using a linear regression model in the total population and in 40 to 49, 50 to 59, and 60 years and older age categories. In the whole population, there was an inverse relationship between pulse pressure and glomerular filtration rate; however, this relation did not persist after adjustment for age. In fact, the inverse relationship between pulse pressure and glomerular filtration rate was only present in patients 60 years of age or older. This relationship in elderly patients remained after adjustment for age, gender, MAP, and cardiovascular risk factors (P=0.006). It is suggested that pulse pressure, a marker of arterial stiffening, may have a detrimental influence on the age-related decline in glomerular filtration rate, after 60 years of age in patients with never-treated isolated systolic hypertension.

Adult↗

PubMed2005

Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index.

BACKGROUND: The Cockcroft-Gault (CG) and simplified Modification of Diet in Renal Disease (MDRD) formulas are the most widely used estimates of renal function. The influence of age and body mass index (BMI) on the performance of these equations was analyzed in 850 subjects with serum creatinine levels less than 1.5 mg/dL (<133 micromol/L). METHODS: Glomerular filtration rate (GFR) was measured as urinary clearance of continuously infused technetium Tc 99m-labeled diethylene triaminopentaacetic acid. Performance was assessed as bias, precision, and accuracy. RESULTS: In the total population, the CG and MDRD calculations based on enzymatic measurement of serum creatinine (which is constantly less than that obtained by using the alkaline picrate [Jaffé] method) significantly underestimated GFR by 4.9 and 12.4 mL/min/1.73 m2 (0.08 and 0.21 mL/s/1.73 m2), respectively. In patients 65 years and older, underestimation by means of the CG formula was enhanced, whereas that by means of the MDRD formula was blunted, compared with the group younger than 65 years (-11.3 versus -3.7 mL/min/1.73 m2 [-0.19 versus -0.06 mL/s/1.73 m2] for CG and -3.7 versus -14.0 mL/min/1.73 m2 [-0.06 versus -0.23 mL/s/1.73 m2] for MDRD). GFR was underestimated to a large extent by means of the MDRD equation irrespective of BMI. Conversely, the underestimation by means of the CG formula found in lean people (-13.0 mL/min/1.73 m2 [-0.22 mL/s/1.73 m2]) was blunted in overweight people (BMI, 25 to 30 kg/m2) and reversed to overestimation (+10.1 mL/min/1.73 m2 [+0.17 mL/s/1.73 m2]) in obese subjects (BMI > 30 kg/m2). CONCLUSION: As suggested by estimations obtained using enzymatic serum creatinine measurement, the MDRD equation may be the estimation of choice in elderly patients, whereas the CG estimate is preferable in subjects younger than 65 years. Nevertheless, when obesity is present, no reliable estimation can be obtained by using the CG or MDRD formula.

Adolescent↗

PubMed2005

Determinants of cardiorenal damage progression in normotensive and never-treated hypertensive subjects.

BACKGROUND: In the present longitudinal study, we attempted to identify the determinants of cardiorenal damage progression in normotensive subjects (<140/90 mm Hg) and patients with never-treated essential hypertension. METHODS: Renal hemodynamics and function and cardiac morphology were evaluated by isotopic techniques and echocardiography at baseline and after a median follow-up period of 5.2 years (range 3 to 13) in 30 normotensive and 33 hypertensive subjects. RESULTS: The results are mean +/- SD. Among normotensive subjects at baseline, 50% became hypertensive during follow-up. In the whole population, multivariate analysis showed that age was the main determinant of the progression of systolic blood pressure. The yearly change in glomerular filtration rate (GFR) was exaggerated in hypertensive when compared to normotensive subjects at baseline (-1.22 +/- 2.71 vs. 0.12 +/- 2.08 mL/min/year, respectively) (P= 0.033). In the whole population, only baseline systolic blood pressure remained correlated to the change in GFR, independently of GFR at baseline (model r(2)= 0.44) (P < 0.0001). The observed increase in albuminuria was correlated with change in blood pressure only in hypertensive subjects at baseline. Left ventricular mass (LVM) progression was significant only in men and its determinants were basal plasma aldosterone, serum uric acid, and triglyceride and change in systolic blood pressure (r(2)= 0.71) (P < 0.0001). CONCLUSION: In a population of untreated subjects, baseline blood pressure as well as progression of blood pressure during follow-up are the main determinants of the decline in GFR, progression of albuminuria, and LVM.

Adolescent↗

PubMed2005

Prevention and reversal by enalapril of target organ damage in angiotensin II hypertension.

Angiotensin-converting enzyme inhibitors (ACE-Is) prevent target organ damage in several models of hypertension. The aim of this study was to assess the influence of the ACE-I enalapril (10 mg/kg(-1) per day, gavage) on the cardiovascular alterations and production of free radicals induced by chronic infusion of angiotensin II (Ang II, 200 ng/kg(-1) per minute, s.c.) in Sprague-Dawley rats. Enalapril was given concomitantly for the 10 days of Ang II infusion (prevention) or from day 10 to 17 of Ang II infusion (intervention). The influence of the NADPH oxidase inhibitor apocynin (600 mg/L(-1) in drinking water) was evaluated. Enalapril and apocynin had no effect on hypertension in the prevention and intervention studies. Enalapril prevented the increase in heart weight index (HWI), carotid cross-sectional area (CSA) and albuminuria induced by Ang II. Enalapril reduced HWI and albuminuria whereas CSA was not affected in the intervention study. Apocynin had effects comparable to enalapril. Both enalapril and apocynin reduced the overproduction of superoxide anion by the left ventricle and rise in advanced oxidation protein products induced by Ang II. Therefore, the antioxidant but not the antihypertensive effect of enalapril may participate in the prevention and treatment of the Ang II-induced cardiovascular and renal alterations.

Acetophenones↗

PubMed2004

Heterogeneity of cardiorenal characteristics in normotensive subjects.

Blood pressure is a marker of elevated risk for cardiovascular disease, even within the normotensive range. The present study evaluates cardiorenal modifications observed in normotensive (<140/90 mm Hg) subjects. Using World Health Organization-International Society of Hypertension definitions, 265 normotensive subjects were categorized as having optimal (n=73), normal (n=84), and high-normal (n=108) blood pressure. Renal hemodynamics and function and cardiac morphology were evaluated by isotopic clearance techniques and ultrasonography, respectively. Urinary albumin excretion was measured in 24-hour urine collections. Body mass index and 24-hour urinary sodium (estimate of sodium intake), as well as left ventricular mass index, relative wall thickness, and glomerular filtration rate and filtration fraction, progressively increased in the optimal to high-normal groups. In contrast, effective renal plasma flow remained constant. Albuminuria was similar in all groups. Of interest, the proportion of subjects with concentric pattern of cardiac geometry (relative wall thickness > or =0.44) increased from 7% in optimal to 13% and 20% in normal and high-normal groups, respectively (P<0.05). Within this normotensive range of blood pressure, left ventricular mass index and relative wall thickness but not albuminuria were linearly correlated to systolic blood pressure; however, no correlation with diastolic blood pressure was found. In conclusion, changes in cardiac geometry and renal hemodynamics (increase in glomerular filtration rate and filtration fraction, an approximate index of glomerular pressure) that could predispose to cardiovascular morbidity and renal risk are already present in normotensive subjects with blood pressure higher than 120/80 mm Hg.

Adolescent↗

PubMed2004

Systemic and renal effect of chronic omapatrilat in sodium-restricted, one-kidney, one-clip hypertensive rats.

OBJECTIVE: The systemic and renal effect of omapatrilat was evaluated and compared with that of enalapril (30 and 10 mg/kg per day) in sodium-depleted, one-kidney, one-clip hypertensive rats. Participation of kinins was assessed by concomitant infusion of Hoe140 (300 microg/kg per day). DESIGN: Four weeks after clipping and uninephrectomy, dietary sodium was withdrawn for 2 weeks and rats were treated during the last 6 days of the study. METHODS: Tail-cuff pressure and sodium excretion were determined in conscious rats. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined in anesthetized rats using clearance methods. The heart weight index was calculated. RESULTS: Omapatrilat was as effective as enalapril in reducing arterial pressure, and Hoe140 had no influence. Natriuresis increased to a similar extent with omapatrilat and enalapril. Hoe140 prevented the sodium loss only in enalapril-treated rats. Compared with untreated rats, GFR was reduced to a lesser extent by omapatrilat than enalapril (694 +/- 93 and 364 +/- 40 versus 848 +/- 43 microl/min per g kidney weight). Hoe140 had no influence on GFR in omapatrilat-treated animals but attenuated the reduction of GFR in enalapril-treated rats (662 +/- 22 and 543 +/- 62 microl/min per g kidney weight). Since RPF was not significantly affected, reduction of the filtration fraction was more marked in enalapril- than omapatrilat-treated rats (60 and 28%, respectively). Heart weight index was lower in omapatrilat-treated rats than in untreated or enalapril-treated rats. Hoe140 failed to significantly obliterate the antihypertrophic effect of omapatrilat. CONCLUSION: These results suggest that accumulation of natriuretic peptides due to neutral endopeptidase inhibition participated in the antihypertrophic effect of omapatrilat and tended to counteract the deleterious effect of ACE inhibition on renal function.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Dietary sodium and pulse pressure in normotensive and essential hypertensive subjects.

OBJECTIVES: To assess the influence of sodium intake on the two components of arterial blood pressure [mean blood pressure (MBP) and pulse pressure] and left ventricular mass (LVM) in normotensive subjects and never-treated hypertensive patients. METHODS: Blood pressure, LVM (M-mode echocardiography) and sodium excretion as an index of dietary sodium were measured in 459 males and 396 females, aged 14-93 years, with elevated (63% of population) or normal blood pressure. RESULTS: Because pulse pressure decreased with age up to approximately 40 years of age, and increased thereafter, analysis was undertaken separately in 438 young (age < or = 40 years) and 417 middle-aged to elderly subjects. Before age 40 years, only pulse pressure was independently and positively influenced by urinary sodium excretion. After age 40 years, MBP and LVM index but not pulse pressure were positively influenced by urinary sodium excretion. When men and women were analysed separately according to tertiles of urinary sodium excretion, pulse pressure adjusted for MBP and age increased from the first to the third tertile of urinary sodium excretion in males (P < 0.03), but not in females. CONCLUSIONS: The influence of sodium intake on pulse pressure was found in the younger subjects of both males and females and only in men older than 40 years.

Adolescent↗

PubMed2003

Left ventricular remodeling and renal function in never-treated essential hypertension.

In the general population, renal function linearly declines with age; hypertension may accelerate this decline. Because concentric left ventricular (LV) hypertrophy is a strong marker of the severity of hypertension, the influence of LV geometry on the age-associated decline in renal function was assessed in 195 normotensive subjects and 645 patients with never-treated essential hypertension with an average duration of 30 mo. According to LV mass and relative wall thickness, hypertensive patients were divided into normal LV (NL, 48%), concentric remodeling (CR, 19%), and concentric (CH, 22%) and eccentric (EH, 11%) hypertrophy. GFR and effective renal plasma flow (ERPF) were estimated by isotopic clearance technique. GFR and ERPF were inversely correlated with age in normotensive and hypertensive subjects, and no marked influence of the BP level or the presence of LV hypertrophy was detected. However, the slope of the regression line of GFR versus age was accentuated (P < 0.01) in patients with CH or CR (slope values of -0.95 +/- 0.11, -0.86 +/- 0.14 ml/min per yr, respectively) when compared with patients with EH or NL (slope values of -0.58 +/- 0.16 and -0.58 +/- 0.08 ml/min per yr, respectively). No such results were obtained when creatinine clearance was considered. Urinary albumin excretion was higher in patients with concentric or eccentric LV hypertrophy than in patients with concentric LV remodeling or normal LV. These results demonstrate that in never-treated essential hypertension, the age-associated decline in GFR is markedly influenced by the concentric pattern of LV response to hypertension rather than the level of BP and/or the presence of LV hypertrophy.

Adolescent↗

PubMed2003

Candesartan: nephroprotective effects and treatment of diabetic nephropathy.

Candesartan shows beneficial end-organ effects in the kidney. Some of these appear to be related not to the reduction in systemic blood pressure induced by candesartan, but to its blockage of intrarenal angiotensin II type I (AT1) receptors. Initial studies have shown that renal vascular resistance was reduced in patients with hypertension receiving candesartan, and urinary albumin excretion was reduced in patients with type 2 diabetes mellitus and concomitant microalbuminuria or proteinuria. These findings, together with the results of recently published large randomized studies involving diabetic patients with hypertension treated with other angiotensin II receptor blockers, indicate that this class of drugs is beneficial in preventing the development or progression of diabetic nephropathy. This review summarizes the large body of findings related to these renoprotective effects and reported during experimental and clinical research on candesartan for the treatment of diabetic nephropathy.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2002

Sodium restriction prevents cardiac hypertrophy and oxidative stress in angiotensin II hypertension.

The influence of a low-sodium (LS) diet was assessed on the cardiac and renal alterations and pro-oxidant effect associated with a 10-day infusion of angiotensin II (200 or 400 ng. kg(-1). min(-1), osmotic pumps). Tail-cuff pressure (TCP), albuminuria, and renal blood flow were determined at the end of the experiments. Heart weight index (HWI) and production of superoxide anion (O(2)(-).) by the left ventricle and H(2)O(2) by the aorta was measured with the use of bioluminescence. Although the final TCP was similar in LS and normal sodium (NS) rats infused with high and low doses of angiotensin II, respectively, the increase in HWI was prevented by the LS diet. Sodium restriction reduced the rise in albuminuria without a change in the renal effect of angiotensin II. The increased production of O(2)(-). and H(2)O(2) observed in NS rats was abrogated in LS rats. The beneficial influence of dietary sodium restriction on target organ damage induced by angiotensin II is independent of arterial pressure reduction and possibly related to attenuation of the prooxidant effect of the peptide.

Albuminuria↗

PubMed2002

Dietary sodium and target organ damage in essential hypertension.

In addition to its widely contested influence on arterial pressure, dietary sodium may exert some nonpressure-related effects on left ventricular mass in humans. In the present study, we hypothesized that sodium intake (estimated by two consecutive measurements of 24-h urinary sodium excretion) may amplify the effect of arterial pressure on target organ damage (ie, left ventricular mass and microalbuminuria) in a large group of normotensive subjects and patients with never-treated uncomplicated essential hypertension. Left ventricular mass (M-mode echocardiography) and urinary albumin excretion were assessed in 839 subjects (471 men and 368 women) aged 15 to 70 years, with elevated (60%) or normal arterial pressure. In the entire population, multivariate analysis indicated that the relationship between urinary sodium excretion and left ventricular mass index (beta = 0.02, P < .01) as well as urinary albumin excretion (beta = 0.001, P < .0001) was independent from sex, age, body mass index, and systolic arterial pressure. When subjects were divided into quintiles according to urinary sodium excretion, left ventricular mass index and urinary albumin excretion increased significantly from the lowest to the highest quintile in both genders, despite similar values of systolic arterial pressure. The slope of the regression line linking systolic arterial pressure to left ventricular mass index (in men) and urinary albumin excretion (in the entire population) obtained within each quintile of urinary sodium excretion, progressively and linearly increased from the lowest to the highest quintile. These results suggest that sodium intake may amplify the effect of arterial pressure on both the left ventricle and the kidney, and thus suggest that dietary sodium may be an independent factor of cardiovascular risk.

Adolescent↗

PubMed2002

Pathophysiologic and therapeutic importance of tissue ACE: a consensus report.

Angiotensin-converting enzyme (ACE) activation and the de novo production of angiotensin II contribute to cardiovascular disease through direct pathological tissue effects, including vascular remodeling and inflammation, as well as indirect action on nitric oxide bioavailability and its consequences. The endothelium plays a pivotal role in both vascular function and structure; thus, the predominant localization of ACE to the endothelium has implications for the pathobiology of vascular disease, such as coronary artery disease. Numerous experimental studies and clinical trials support the emerging realization that tissue ACE is a vital therapeutic target, and that its inhibition may restore endothelial function or prevent endothelial dysfunction. These effects exceed those attributable to blood pressure reduction alone; hence, ACE inhibitors may exert an important part of their effects through direct tissue action. Pharmacologic studies show that while ACE inhibitors may differ according to their binding affinity for tissue ACE the clinical significance remains to be determined.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Simvastatin prevents angiotensin II-induced cardiac alteration and oxidative stress.

The influence of the HMG-CoA reductase inhibitor simvastatin was assessed on the cardiovascular alterations and production of free radicals associated with chronic angiotensin II (Ang II) infusion. Simvastatin (60 mg/kg per day PO) or placebo were given concomitantly for 10 days in Sprague-Dawley rats infused with Ang II (200 ng/kg per minute SC, osmotic pump). In addition, simvastatin or placebo was also given in vehicle-infused rats. Tail-cuff pressure and albuminuria were measured before and at the end of the treatment period. Cardiac weight, carotid structure, production of reactive oxygen species (ROS, by chemiluminescence) by polymorphonuclear leukocytes and aortic wall as well as protein and lipid oxidation products were determined at the end of the study. Ang II increased tail-cuff pressure by 56+/-12 mm Hg and simvastatin blunted the development of hypertension by approximately 70% (19+/-5 mm Hg). Increases in heart weight index and carotid cross-sectional area induced by Ang II were obliterated by simvastatin (3.18+/-0.09 versus 3.46+/-0.11 mg/g body wt and 0.125+/-0.010 versus 0.177+/-0.010 mm2, respectively). The Ang II-induced increases in leukocyte and aortic production of ROS as well as protein and lipid oxidation products were prevented by simvastatin. No effect of simvastatin was detected in non-Ang II-infused rats. These results indicate that simvastatin prevented the development of hypertension and cardiovascular hypertrophy together with inhibition of the induced angiotensin II production of ROS. Therefore, inhibition of HMG CoA reductase by statins may have a beneficial effect on cardiovascular alterations through its antioxidant action in experimental Ang II-dependent hypertension.

Angiotensin II↗

PubMed2002

Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study.

Genes may modulate the changes of blood pressure (BP) with age; this possibility has never been studied for the age-related increase of pulse pressure (PP), although in older populations, PP is considered the stronger mechanical factor predicting cardiovascular mortality. In humans, the presence of the mutant allele C of the angiotensin II (Ang II) AT(1)-receptor or of the mutant allele T of the eNOS G(298) T gene polymorphisms is associated with enhanced contractile properties of conduit arteries in response to vasoconstrictive agents. In this study, we evaluated, in subjects with untreated essential hypertension, whether the presence of these mutant alleles or their combination might influence the age-related increase of PP. Three main findings emerged from the study and were particularly observed in women: 1) the presence of the C and/or of the T mutant alleles or their combination were associated with a steeper slope of the age versus PP curve, compared with subjects without the mutant allele; 2) the slope was more significantly enhanced when the two mutant alleles were associated in the same genotype; and 3) no comparable age- and gender-related changes in systolic, diastolic or mean BP were found according to this genetic classification. In subjects with essential hypertension, genes may modulate the age-mediated increase of PP. This finding gives new insights in the interactions between genes, mechanical factors and cardiovascular risk.

Aging↗